Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity

Manish Sethi, Rohit Sukumar, Shrirang Karve, Michael E. Werner, Edina C. Wang, Dominic T. Moore, Sonya R. Kowalczyk, Liangfang Zhang, Andrew Z. Wang

Research output: Contribution to journalArticlepeer-review

45 Scopus citations

Abstract

The effects of nanoparticle (NP) properties, such as size, shape and surface charge, on their efficacy and toxicity have been studied extensively. However, the effect of controlled drug release on NP efficacy and toxicity has not been thoroughly evaluated in vivo. Our study aims to fill this knowledge gap. A key challenge in characterizing the relationship between drug release and therapeutic ratio is to fabricate NPs that differ only in their drug release profile but are otherwise identical. To overcome this challenge, we developed crosslinkable lipid shell (CLS) NPs, where the drug release kinetics can be modulated without changing any other NP property. Using CLS NPs with wortmannin and docetaxel as model drugs, we determined the relationship between the release kinetics and therapeutic efficacy and toxicity of the drugs. We have determined that drug release kinetics can affect the therapeutic efficacy of NP docetaxel and NP wortmannin in vitro and in vivo. Our study also demonstrates that a decrease in drug release kinetics can result in a decrease in the hepatotoxicity of CLS NP wortmannin. Using two model drugs, the current findings provide the first direct evidence that NP drug release profile is a critical factor in determining the NP therapeutics' efficacy and toxicity in vivo.

Original languageEnglish (US)
Pages (from-to)2321-2327
Number of pages7
JournalNanoscale
Volume6
Issue number4
DOIs
StatePublished - Feb 21 2014
Externally publishedYes

ASJC Scopus subject areas

  • Materials Science(all)

Fingerprint

Dive into the research topics of 'Effect of drug release kinetics on nanoparticle therapeutic efficacy and toxicity'. Together they form a unique fingerprint.

Cite this